an antimicrotubule agent isolated from the bark of Taxus brevifolia, Rowinsky, E. K.; Donehower, R. C., Pharmac. Ther. 1991, 52, 35, has recently attracted much attention because of its efficacy in the treatment of various types of cancer, (a) Slichenmyer, W. J.; Van Hoff, D. D., Anti-Cancer Drugs, 1991, 2, 519; (b) Rowinsky, E. K.; Donehower, R. C. J., Natl. Cancer Inst., 1991, 83 1778; (c) Holes, F. A.; Walters, R. S.; Theriault, R. L.; Forman, A. D.; Newton, L. K.; Raber, M. N.; Buzdar, A. U.; Frye, D. K.; Hortobagyi G. N., Ibid. 1991, 83, 1797. However, one major impediment to the wide use of taxol in cancer chemotherapy is its extremely limited availability. Also, chemical complexity has prohibited the commercial production of taxol by total synthesis, (a) Kingston, D. G. I.; Samaranayake, G.; Ivey, C. A., J. Nat. Prod., 1990, 53, 1; (b) Kingston, D. G. I., Pharmac. Ther., 1991, 52, 1. Thus, a viable approach for the preparation of taxol is to utilize more accessible baccatin III or 10-deacetylbaccatin III ##STR2## as precursor via a semisynthetic route, (a) Denis, J. -N; Greene, A. E.; Guenard, D.; Gueritte-Voegelein, F.; Mangatal, L.; Potier, P., J. Am. Chem. Soc., 1988, 110, 5917; (b) Holton, R. A., U.S. Pat. No. 5,015,744, (Chem. Abst., 1991, 115, 159485).
As the importance of the C-13 side chain, the N-benzoyl-(2R, 3S)-phenylisoserine, moiety, ##STR3## where R=H or CH.sub.3 for the biological activity of taxol becomes evident, (a) Guenard, D.; Gueritte-Voegelein, F.; Lavelle, F.; Le Goff, M. T.; Mangatal, L.; Potier, P., J. Med. Chem., 1991, 34, 992; (b) Swindell, C. S.; Krauss, N. E.; Horwitz, S. B.; Ringel, I., Ibid, 1991, 34, 1176, enantioselective synthesis of N-Benzoyl-(2R,2S)-3-Phenylisoserine has been the focus of many investigations. A variety of strategies employing Sharpless epoxidation, Denis, J. -N; Greene, A. E.; Serra, A. A.; Luche, M.-J., J. Org. Chem., 1986, 51, 46, asymmetric dihydroxylation, Denis, J. -N.; Correa, A.; Greene, A. E., J. Org. Chem., 1990, 55, 1957, enzymatic resolution, (a) Honig, H.; Seufer-Wasserthal, P.; Weber, H. Tetrahedron, 1990, 46, 3841; (b) Honig, H.; Seufer-Wasserthal; Weber, H., Tetrahedron Lett., 1990, 31, 3011, a chiral precursor, Denis, J. -N.; Correa, A.; Greene, A. E., J. Org. Chem., 1991, 56, 6939, and asymmetric ester enolate-imine cyclocondensation, Ojima, I.; Habus, I.; Zhao, M; Georg. G. I.; Jayasinghe, L. R. J. Org. Chem., 1991, 56, 1681, have been reported.
The present invention embodies a facile approach using enzymatically-prepared chiral trans-.beta.-phenylglycidic esters as the starting material for the synthesis of the taxol C-13 side chain.